Abstract

A103

Analyses of candidate diagnostic biomarkers in intact tissues represent a critical component in the development of therapeutics. In oncology drug development, entire signaling pathways are profiled with a variety of high-throughput techniques. However, in the field of histology, tissue-based diagnostics (IHC and ISH) are generally dominated by single- or dual-analyte tests. In addition, manual methods for slide processing promote inconsistency, are labor demanding and time-consuming. Ventana Medical Systems has developed automated platforms for conducting IHC and ISH in widely available formalin-fixed paraffin-embedded (FFPE) tissues. These instruments enable rapid evaluation and validation of candidate biomarkers in a high-throughput format. Further, advances in key detection technologies, including Quantum Dots (QDots™) conjugates, hyper-spectral imaging and data analysis platforms, provide a growing set of tools that better complement early biomarker discovery. We have applied these methods to monitor biomarkers used for stratification, and as surrogates of drug response, in growth-factor signaling pathways. We use these examples to demonstrate the utility of coupling high-throughput, automated histochemistry with quantifiable, multiplexed biomarkers. Importantly, these findings are reported for individual cells in their true anatomical context.